Circ_0005372 targets the miR-153-3p/ITGB3 axis to stimulate the PI3K/AKT signaling pathway to facilitate the occurrence and development of congenital heart disease and pulmonary arterial hypertension in children
Congenital heart disease (CHD) arises due to malformations in the cardiovascular system that resulted from abnormal development during the fetal period, combined with the failure of certain tissues to degenerate properly after birth [[1], [2], [3]]. Genetic and environmental factors are the main causes of CHD, and the incidence is between 0.6 % and 1 % in newborns [4]. Once it is not diagnosed in the early stage of the disease or is not treated in time after the onset of the disease, the patients will die from various complications of CHD. As the highest risk complication of CHD, Pulmonary arterial hypertension (PAH) greatly increases the mortality of CHD patients. Additionally, it has been reported that abnormal diffusion of human pulmonary artery smooth muscle cells (HPASMCs) under hypoxia will cause pulmonary artery stenosis or occlusion, and then accelerate the progression of PAH [5]. With the deterioration of CHD-associated PAH (PAH

CHD), persistently elevated pulmonary artery pressure can cause right heart failure and even death [6,7]. Thus, it is imperative to explore more accurate biomarkers and new therapeutic targets for PAH

CHD.CircRNAs constitute a unique category of non-coding RNA molecules, which is a well-established fact. Compared with linear RNA, circRNA molecules show a closed-loop structure, have higher stability, and are therefore less susceptible to degradation [8]. Recent studies have elucidated that circRNAs harbor binding sites for microRNAs (miRNAs), functioning as a sponge to sequester these miRNAs and thereby relieve their inhibitory effects on target genes. It is due to this mechanism that circRNAs have been clarified to interact with miRNAs to regulate the occurrence and development of various diseases [[9], [10], [11]]. Interestingly, relevant literature reported that there were many differentially expressed circRNAs in neonatal PAH

CHD patients [12].MiRNAs are endogenous small RNAs that serve as an essential factor in gene expression, either at the translational or the transcriptional level [13]. At present, more and more studies have shown that the miRNAs family has a crucial relationship with the development of PAH [14,15]. Hu F et al. proved that miRNA-30d-5p adjusted the apoptosis of HPASMCs by targeting the Notch-3 signaling pathway [16]. It was confirmed that miR-153 targets ROCK1 and NFATc3 to abolish abnormal proliferation and metastasis of HPASMCs caused by hypoxia [17]. However, there are few studies on the function and mechanism of circRNAs in PAH

CHD. Our research aims to clarify the relationship between circRNAs and miRNAs and circRNAs involved in PAH

CHD pathogenesis.
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